Scientists have successfully transplanted human chromosomes into mice, a first that promises to transform medical research into the genetic causes of disease. The mice were genetically engineered to carry a copy of human chromosome 21, a string of about 250 genes. About one in a thousand people are born with an extra copy of the chromosome, a genetic hiccup that causes Down's syndrome.

Genetic studies of the mice will help scientists to nail down which genes give rise to medical conditions which are prevalent among people with Down's syndrome, such as impaired brain development, heart defects, behavioural abnormalities, Alzheimer's disease and leukaemia.

Medical researchers yesterday hailed the work as a "tour de force", but critics accused the team of pushing the boundaries of genetic manipulation too far and blurring the distinction of what was biologically human.

Elizabeth Fisher at the Institute of Neurology and Victor Tybulewicz at the National Institute for Medical Research in London spent 13 years perfecting the technique which is reported in the journal Science today.

To create the mice, the team first extracted chromosomes from human cells and squirted them on to beds of stem cells taken from mouse embryos. Any stem cells that absorbed human chromosome 21 were injected into three-day-old mouse embryos which were then re-implanted into their mothers. The newly born mice carried copies of the chromosome and were able to pass it on to their own young.

"By adding the chromosome, we have mice that show nearly all of the characteristics of Down's syndrome in humans," said Dr Fisher. "It means we can tease out the genes that give rise to the different aspects of Down's syndrome, because we know we've got the right genes in there."

According to Dr Tybulewicz, genetic tests on the mice, which will systematically knock out different genes on the transplanted chromosome, will help identify which gene or genes cause each of the symptoms common to people with Down's syndrome. "This should illuminate which genes lead to heart defects, the higher risk of leukaemia and early onset Alzheimer's," he said.

Peter Scambler, a molecular geneticist at the Institute of Child Health in London, said: "This is a technical tour de force. It's difficult to envisage how one could otherwise tackle something as complex as Down's syndrome, because we can't go around creating human embryos with the condition."

Steve Brown, director of the Medical Research Council's mammalian genetics unit, said: "This will tell us a lot about which genes are key to the myriad abnormalities we associate most with Down's syndrome. We are taking a step forward in the tools we have to investigate the genetic basis of these conditions."

But according to David King, of the pressure group Human Genetics Alert, the potential breakthrough comes at too high a cost. "Creating organisms with whole chromosomes from another species is genetic engineering taken to another level.

"Before, researchers have said they're not making big changes because they're only inserting the odd gene into animals. If you're talking about creating something with a whole human chromosome in it, you have to ask is this really a mouse any more? Is it starting to be a new species, a hybrid between a mouse and a human? If more chromosomes are put in, are we going to have to start giving these things pseudo human rights?"

Dr King said the research could lead to technologies that would allow humans to be genetically engineered. "Once Britain has a clear ban on human genetic engineering, I'll be much happier for scientists to do these studies with mice. But they're developing techniques that could be applied to human beings and, in essence, that leads to a new form of eugenics," he said.

Dr Fisher said the transferring of a chromosome was merely a more effective way of swapping large numbers of genes into an animal to benefit medical testing. "We're not trying to humanise mice, we're trying to tease out the genetics of a very complex disorder."

Dr Tybulewicz added: "There's nothing more obviously humanlike about these mice than any others. If you were to see them, you'd not be able to tell they are different to a normal one."

Carol Boys of the Down's Syndrome Association said she welcomed the research if it would lead to an improvement in the lives of people with Down's syndrome. "Any research that could lead to a greater understanding of why people with Down's syndrome are more susceptible to certain medical conditions is important. However, this research does not herald a 'cure' or a 'treatment' for Down's syndrome."

Footnotes

Chromosomes

Humans have 23 pairs of chromosomes, each a continuous strand of tightly coiled DNA, which together contain our entire complement of genes. The two sexes share 22 of the pairs, but the 23rd pair, the sex chromosomes, differ, with women having two X chromosomes and men having one X and one Y chromosome.

Down's syndrome

People born with three copies of chromosome 21 instead of the usual two develop Down's syndrome. About 60,000 people have it in the UK. People with Down's syndrome typically have craniofacial abnormalities, impaired brain development and are at a greater risk of leukaemia, heart defects and Alzheimer's disease. They can expect to live to between 40 and 60.

Stem cells

In the first few days of their existence, embryos contain stem cells that can form any of the tissues needed to make an entire organism, including bone, skin, muscle or nervous tissue.

Knock out

One of the most common ways to find out what a gene does in an animal is to knock it out. When scientists knock out a gene they silence it, so that it is in effect missing from the animal. Comparing animals with and without the gene helps reveal the role of the gene.

Eugenics

The science of using controlled breeding to increase the occurrence of desirable heritable characteristics in a population.